Imputation of a true endpoint from a surrogate: application to a cluster randomized controlled trial with partial information on the true endpoint

The aim of this paper was to estimate the treatment effect using data from every practice in the study. Where the true endpoint was not available, it was estimated by three approaches, a regression method, multiple imputation and a full likelihood model.Including the surrogate data in the analysis yielded an estimate of the treatment effect which was more precise than an estimate gained from using the true end point data alone.The full likelihood method provides a new imputation tool at the disposal of trials with surrogate data.The Anglia Menorrhagia Education Study (AMES) [1,2] is a randomized controlled trial which tested the effectiveness of an "academic detailing" education package [3] in primary care and hospital gynaecology units to improve the management of women with menorrhagia (excessive menstrual bleeding). Here we are concerned with the first phase of this trial and only consider data from primary care.The general practice was the unit of randomization and the primary outcome measure of interest was the proportion of referrals of women with menorrhagia to hospital. In this part of the trial, data were collected in two ways. Firstly the doctors in the practices in the study were asked to keep a record of consultations for menorrhagia, with outcome of consultation, on supplied data sheets. We refer to this as the reported data. Secondly, an audit of 52% of the practices was performed after the trial was over. This was performed in order to have an objective measure of referral which did not depend on a busy practitioner reporting. 52% of the practices was considered enough for sufficient power having seen the reported data. The reported data was only recorded for one year post-intervention, whereas one-year pre-intervention data was also available for the audited part of the trial. Total numbers of patients seen and patients referred for the reported and audits phase are given in Table 1. This paper is concerned with combining the reported and audited dat